ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Jyseleca 100 mg film-coated tablets Jyseleca 200 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Jyseleca 100 mg film-coated tablets Each film-coated tablet contains filgotinib maleate equivalent to 100 mg of filgotinib. Excipient with known effect Each 100 mg film-coated tablet contains 76 mg of lactose (as monohydrate). Jyseleca 200 mg film-coated tablets Each film-coated tablet contains filgotinib maleate equivalent to 200 mg of filgotinib. Excipient with known effect Each 200 mg film-coated tablet contains 152 mg of lactose (as monohydrate). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet. Jyseleca 100 mg film-coated tablets Beige 12 × 7 mm, capsule-shaped, film-coated tablet debossed with “GSI” on one side and “100” on the other side. Jyseleca 200 mg film-coated tablets Beige 17 × 8 mm, capsule-shaped, film-coated tablet debossed with “GSI” on one side and “200” on the other side. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Jyseleca is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Jyseleca may be used as monotherapy or in combination with methotrexate (MTX). 2 4.2 Posology and method of administration Treatment with filgotinib should be initiated by a physician experienced in the treatment of rheumatoid arthritis. Posology The recommended dose of filgotinib for adult patients with rheumatoid arthritis is 200 mg once daily. Laboratory monitoring, and dose initiation or interruption Guidance for laboratory monitoring, and dose initiation or interruption is provided in Table 1. Treatment should be interrupted if a patient develops a serious infection until the infection is controlled (see section 4.4). Table 1: Laboratory measures and monitoring guidance Laboratory measure Action Monitoring guidance Treatment should not be initiated, Before treatment initiation and or should be interrupted, if ANC is thereafter according to routine Absolute neutrophil count (ANC) < 1 × 109 cells/L. Treatment may patient management be restarted once ANC returns above this value Treatment should not be initiated, or should be interrupted, if ALC is Absolute lymphocyte count (ALC) < 0.5 × 109 cells/L. Treatment may be restarted once ALC returns above this value Treatment should not be initiated, or should be interrupted, if Hb is Haemoglobin (Hb) < 8 g/dL. Treatment may be restarted once Hb returns above this value 12 weeks after initiation of Patients should be managed treatment and thereafter according Lipid parameters according to international clinical to international clinical guidelines guidelines for hyperlipidaemia for hyperlipidaemia Special populations Elderly A starting dose of 100 mg once daily is recommended for patients aged 75 years and older as clinical experience is limited. Renal impairment No dose adjustment is required in patients with mild renal impairment (creatinine clearance [CrCl] ≥ 60 mL/min). A dose of 100 mg of filgotinib once daily is recommended for patients with moderate or severe renal impairment (CrCl 15 to < 60 mL/min). Filgotinib has not been studied in patients with end stage renal disease (CrCl < 15 mL/min) and is therefore not recommended for use in these patients (see section 5.2). Hepatic impairment No dose adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh A or B). Filgotinib has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is therefore not recommended for use in these patients (see section 5.2). Paediatric population The safety and efficacy of filgotinib in children under the age of 18 years have not yet been established. No data are available. 3 Method of administration Oral use. Jyseleca can be taken with or without food (see section 5.2). It has not been studied if tablets can be split, crushed, or chewed, and it is recommended that tablets are swallowed whole. 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Active tuberculosis (TB) or active serious infections (see section 4.4). Pregnancy (see section 4.6). 4.4 Special warnings and precautions for use Immunosuppressive medicinal products Combination of filgotinib with other potent immunosuppressants such as azathioprine, ciclosporin, tacrolimus, biologic DMARDs (bDMARDs) or other Janus kinase (JAK) inhibitors is not recommended as a risk of additive immunosuppression cannot be excluded. Infections Infections, including serious infections, have been reported in patients receiving filgotinib. The most frequent serious infection reported with filgotinib was pneumonia (see section 4.8). Among opportunistic infections, TB, oesophageal candidiasis, and cryptococcosis were reported with filgotinib. The risks and benefits of treatment should be considered prior to initiating filgotinib in patients: • with chronic or recurrent infection • who have been exposed to TB • with a history of a serious or an opportunistic infection • who have resided or travelled in areas of endemic TB or endemic mycoses; or • with underlying conditions that may predispose them to infection. Patients should be closely monitored for the development of signs and symptoms of infections during and after filgotinib treatment. If an infection develops during treatment with filgotinib, the patient should be carefully monitored and filgotinib treatment should be temporarily interrupted if the patient is not responding to standard antimicrobial therapy. Filgotinib treatment may be resumed once the infection is controlled. As there is a higher incidence of serious infections in the elderly aged 75 years and older, caution should be used when treating this population. Tuberculosis Patients should be screened for TB before initiating filgotinib. Filgotinib should not be administered to patients with active TB (see section 4.3). In patients with latent TB, standard antimycobacterial therapy should be initiated before administering filgotinib. Patients should be monitored for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating treatment. 4 Viral reactivation Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies (see section 4.8). If a patient develops herpes zoster, filgotinib treatment should be temporarily interrupted until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed in accordance with clinical guidelines before starting and during treatment with filgotinib. Patients who were positive for both hepatitis C antibody and hepatitis C virus RNA were excluded from clinical studies. Patients who were positive for hepatitis B surface antigen or hepatitis B virus DNA were excluded from clinical studies. Malignancy The risk of malignancies is increased in patients with rheumatoid arthritis. Immunomodulatory medicinal products may increase the risk of malignancies. The clinical data are insufficient to assess the potential incidence of malignancies following exposure to filgotinib. Long-term safety evaluations are ongoing. Malignancies were observed in clinical studies of filgotinib. The risks and benefits of filgotinib treatment should be considered prior to initiating treatment in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing filgotinib treatment in patients who develop a malignancy. Non-melanoma skin cancer NMSCs have been reported in patients treated with filgotinib. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Fertility In animal studies, decreased fertility, impaired spermatogenesis, and histopathological effects on male reproductive organs were observed (see section 5.3). The potential effect of filgotinib on sperm production and male fertility in humans is currently unknown. The reversibility of these potential effects is unknown. The potential risk of reduced fertility or infertility should be discussed with male patients before initiating treatment. Haematological abnormalities ANC < 1 × 109 cells/L (see section 4.8) and ALC < 0.5 × 109 cells/L were reported in ≤ 1% of patients in clinical studies. Treatment should not be initiated, or should be temporarily interrupted, in patients with an ANC < 1 × 109 cells/L, ALC < 0.5 × 109 cells/L or haemoglobin < 8 g/dL observed during routine patient management (see section 4.2). Vaccinations Use of live vaccines during, or immediately prior to, filgotinib treatment is not recommended. It is recommended that immunisations be updated in agreement with current immunisation guidelines prior to initiating filgotinib treatment. Lipids Treatment with filgotinib was associated with dose-dependent increases in lipid parameters, including total cholesterol, and high-density lipoprotein (HDL) levels, while low-density lipoprotein (LDL) levels were slightly increased (see section 4.8). LDL cholesterol returned to pre-treatment